G. Lenz, M.D., G. Wright, Ph.D., S.S. Dave, M.D., W. Xiao, Ph.D., J. Powell, M.S., H. Zhao, M.S., W. Xu, M.S., B. Tan, M.D., N. Goldschmidt, M.D., J. Iqbal, Ph.D., J. Vose, M.D., M. Bast, B.S., K. Fu, M.D., Ph.D., D.D. Weisenburger, M.D., T.C. Greiner, M.D., J.O. Armitage, M.D., A. Kyle, Ph.D., L. May, Ph.D., R.D. Gascoyne, M.D., J.M. Connors, M.D., G. Troen, Ph.D., H. Holte, M.D., Ph.D., S. Kvaloy, M.D., Ph.D., D. Dierickx, M.D., G. Verhoef, M.D., J. Delabie, M.D., E.B. Smeland, M.D., Ph.D., P. Jares, Ph.D., A. Martinez, M.D., A. Lopez-Guillermo, M.D., E. Montserrat, M.D., E. Campo, M.D., R.M. Braziel, M.D., T.P. Miller, M.D., L.M. Rimsza, M.D., J.R. Cook, M.D., B. Pohlman, M.D., J. Sweetenham, M.D., R.R. Tubbs, M.D., R.I. Fisher, M.D., E. Hartmann, M.D., A. Rosenwald, M.D., G. Ott, M.D., H.-K. Muller-Hermelink, M.D., D. Wrench, M.D., T.A. Lister, M.D., E.S. Jaffe, M.D., W.H. Wilson, M.D., Ph.D., W.C. Chan, M.D., L.M. Staudt, M.D., Ph.D., for the Lymphoma/Leukemia Molecular Profiling Project
Background The addition of rituximab to combination chemotherapywith cyclophosphamide, doxorubicin, vincristine, and prednisone(CHOP), or R-CHOP, has significantly improved the survival ofpatients with diffuse large-B-cell lymphoma. Whether gene-expressionsignatures correlate with survival after treatment of diffuselarge-B-cell lymphoma is unclear.
Methods We profiled gene expression in pretreatment biopsy specimensfrom 181 patients with diffuse large-B-cell lymphoma who receivedCHOP and 233 patients with this disease who received R-CHOP.A multivariate gene-expression–based survival-predictormodel derived from a training group was tested in a validationgroup.
Results A multivariate model created from three gene-expressionsignatures — termed "germinal-center B-cell," "stromal-1,"and "stromal-2" — predicted survival both in patientswho received CHOP and patients who received R-CHOP. The prognosticallyfavorable stromal-1 signature reflected extracellular-matrixdeposition and histiocytic infiltration. By contrast, the prognosticallyunfavorable stromal-2 signature reflected tumor blood-vesseldensity.
Conclusions Survival after treatment of diffuse large-B-celllymphoma is influenced by differences in immune cells, fibrosis,and angiogenesis in the tumor microenvironment.
Source Information
The affiliations of the authors are listed in the Appendix.
Address reprint requests to Dr. Staudt at the Metabolism Branch, Center for Cancer Research, National Cancer Institute, Bldg. 10, Rm. 4N114, National Institutes of Health, Bethesda, MD 20892, or at lstaudt{at}mail.nih.gov.
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